Distribution of repeat unit differences between alleles at tandem repeat microsatellite loci

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:133421

Jin, L ^[1]; Zhong, Y; Chakraborty, R ^[2]

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1. Univ. Texas Houston Health Science Center, Houston, TX (United States)
2. Univ. Texas Houston Health Center, Houston, TX (United States); and others

PCR-based assays of tandemly repeated microsatellite loci detect genetic variation from which alleles may be scored by their repeat unit lengths. Comparison of allele sizes from such data yields a probability distribution (P{sub k}) of repeat unit differences (k) between alleles segregating in a population. We show that this distribution (P{sub k}; k = 0, 1,2,...) provides insight regarding the mechanism of production of new alleles at such loci and the demographic history of populations, far better than that obtained from other summary measures (e.g., heterozygosity, number of alleles, and the range of allele sizes). The distributions of P{sub k} under multi-step stepwise models of mutation are analytically derived, which show that when a population is at equilibrium under the mutation-drift balance, the distribution of repeat unit differences between alleles is positively skewed with a mode larger than zero. However, when the heterozygosity at a locus is low (say, less than 40%), P{sub k} is a monotonically decreasing function of k. Applications of this theory to data on repeat unit sizes at over 1,240 microsatellite loci from the Caucasians, categorized by the average heterozygosity of loci, indicate that at most microsatellite loci new alleles are produced by stepwise mutations, and this is consistent with the replication slippage mechanism of mutations. The repeat size changes of mutants are probably within one or two units of alleles from which the mutants arise. Distributions of P{sub k} at microsatellite loci located within genes show evidence of allele size constraints. No significant evidence of recent expansion of population sizes in the Caucasians is detected by the distribution of P{sub k}.

• OSTI ID: 133421
• Report Number(s): CONF-941009--; CNN: Grant GM 41399; Grant GM 45861; Grant NIJ-92-IJ-K024
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN 0002-9297; ISSN AJHGAG
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
99 GENERAL AND MISCELLANEOUS
AMINO ACID SEQUENCE
BIOLOGICAL MARKERS
DNA REPLICATION
GENE MUTATIONS
GENES
GENETIC VARIABILITY
HUMAN POPULATIONS
LENGTH
POLYMERASE CHAIN REACTION
POPULATION DYNAMICS
PROBABILITY
SIZE
STATISTICS